Toxicity of common biocides used in aquaculture to embryos and larvae of Brachymystax tsinlingensis Li.

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC50 ) values of the embryos and larvae were 1.71 and 0.22 mg l-1 for copper and 2.57 and 2.72 mg l-1 for zinc, respectively, whereas the MB LC50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l-1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l-1 for embryos and 0.03, 0.03 and 1.78 mg l-1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l-1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l-1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration.

The Extract of Pinellia Ternata-Induced Apoptosis of Leukemia Cells by Regulating the Expression of Bax, Bcl-2 and Caspase-3 Protein Expression in Mice.

The study aims to lessen the monetary burden on patients and society by decreasing the price of proprietary drugs used in leukemia therapy. Flow cytometry, reverse transcription polymerase chain reaction, western blot, and a patient-derived xenograft mouse model were used to confirm the therapeutic effect of Pinellia ternata extract on leukemia. Three types of leukemia cells (K562, HL-60, and C8166 cell lines) were found to undergo early apoptosis (P ≤ .05) after being exposed to P. ternata extract, as measured by flow cytometry. Reverse transcription polymerase chain reaction results showed that P. ternata extract at both middle (300 µg/mL) and high (500 µg/mL) concentrations was able to down-regulate Bcl-2 and upregulate mRNA expression of Bax and caspase-3. In the patient-derived xenograft mouse model formed by BALB/c-nu/nu nude mice, immunohistochemistry indicated that P. ternata extract effectively suppressed the proliferation of leukemia cells. Therefore, P. ternata extract at 300 µg/mL and 500 µg/mL could effectively inhibit myeloid and lymphocytic leukemia cell proliferation and promote leukemia cell apoptosis by regulating Bax/Bcl-2 and caspase-3.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway.

OBJECTIVE: To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish. METHODS: The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe. RESULTS: The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae. CONCLUSION: KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Effect of acid sphingomyelinase on nonalcoholic fatty liver disease via PPARα- PGC-1α pathway / 中国药理学通报

Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.

Primary adrenal NK/T cell lymphoma: a clinicopathologic analysis of six cases / 中华病理学杂志

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.

The effect of Jiegeng decoction on lipopolysaccharide-induced acute lung injury in mice based on metabolomics / 药学学报

One of the traditional prescriptions for treating lung diseases, Jiegeng decoction (JGT), is still unknown in terms of its chemical makeup and mechanism. In this study, Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT, and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury (ALI) model. The potential biomarkers were screened by fold change (FC) > 1.5 or FC < 0.67 and P < 0.05, and enriched for metabolic pathways. A total of 40 compounds, including triterpenoid saponins, flavonoids and glycosides, were identified by mass spectrometry analysis of JGT. All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2021106). The results showed that JGT improved the lung coefficient, and lung tissue morphology of mice with ALI, lowered the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in bronchoalveolar lavage fluid (BALF), and reduced myeloperoxidase (MPO) content in lung tissue. The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI, among which leukotriene D4, docosapentaenoic acid, hypoxanthine, L-5-oxoproline, and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress, and were enriched in the pathways of glutathione metabolism, purine metabolism, and primary bile acid biosynthesis. This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics, providing an important theoretical basis for the clinical application of JGT.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish.@*METHODS@#The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe.@*RESULTS@#The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae.@*CONCLUSION@#KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review.

BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival. AIM: To investigate the clinical features and survival factors in Chinese patients with PMME. METHODS: The clinicopathological findings of ten cases with PMME treated at Henan Provincial People's Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival. RESULTS: A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [P < 0.001, odds ratio (OR): 2.47, 95% confidence interval (CI): 1.72-3.56] and larger tumor size (P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival (OS) was 11.0 mo (range: 1-204 mo). The multivariate Cox analysis showed both the pT stage [P = 0.005, hazard ratio (HR): 1.70, 95%CI: 1.17-2.47] and LNM (P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival (DFS) was 5.3 mo (range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced pT stage (P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME. CONCLUSION: The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

Prognosis factors for death within 90 days of discharge in patients with acute kidney injury requiring continuous renal replacement therapy after surgery for Stanford type A acute aortic dissection / 中华外科杂志

Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old(HR=2.14, 95%CI: 1.09 to 4.21, P=0.03), high lactate values 12 hours after CRRT(HR=1.13, 95%CI: 1.06 to 1.20, P=0.01) and postoperative EF<45%(HR=2.21, 95%CI: 1.09 to 4.51, P=0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.

Tripterygium wilfordii multiglycoside-induced hepatotoxicity via inflammation and apoptosis in zebrafish.

Tripterygium wilfordii multiglycoside (GTW) is a commonly used compound for the treatment of rheumatoid arthritis (RA) and immune diseases in clinical practice. However, it can induce liver injury and the mechanism of hepatotoxicity is still not clear. This study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism involved. The 72 hpf (hours post fertilization) zebrafish larvae were administered with different concentrations of GTW for three days and their mortality, malformation rate, morphological changes in the liver, transaminase levels, and histopathological changes in the liver of zebrafish larvae were detected. The reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the levels of microRNA-122 (miR-122) and genes related to inflammation, apoptosis, cell proliferation and liver function. The results showed that GTW increased the mortality of zebrafish larvae, while significant malformations and liver damage occurred. The main manifestations were elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), significant liver atrophy, vacuoles in liver tissue, sparse cytoplasm, and unclear hepatocyte contours. RT-PCR results showed that the expression of miR-122 significantly decreased by GTW; the mRNA levels of inflammation-related genes il1ß, il6, tnfα, il10, cox2 and ptges significantly increased; the mRNA level of tgfß significantly decreased; the mRNA levels of apoptosis-related genes, caspase-8 and caspase-9, significantly increased; the mRNA level of bcl2 significantly decreased; the mRNA levels of cell proliferation-related genes, top2α and uhrf1, significantly reduced; the mRNA levels of liver function-related genes, alr and cyp3c1, significantly increased; and the mRNA level of cyp3a65 significantly decreased. In zebrafish, GTW can cause increased inflammation, enhanced apoptosis, decreased cell proliferation, and abnormal expression of liver function-related genes, leading to abnormal liver structure and function and resulting in hepatotoxicity.

Effect of Modifide Wenjingtang on JAK2/STAT3 Signal Pathway and Downstream Factors Protein Expression in Endometriosis Rats / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect and mechanism of modified Wenjingtang on endometriosis （EM） rats with kidney deficiency and blood stasis. Method:The 10 from 105 SPF female healthy SD rats were randomly selected as the blank group. The rest constructed the rat model of kidney deficiency and blood stasis by compound factorial method. After the model was successfully established， 10 rats were randomly selected as the sham operation group， with only laparotomy and no intima suture， and the remaining rats were established with EM kidney deficiency and blood stasis type by autologous intimal transplantation. Fifty rats which were randomly selected from 56 successful rats were treated with the modified Wenjingtang （5，10，20 g·kg^-1） and danazol group（63 mg·kg^-1）， 1 time daily ， for 4 weeks. The endometrial tissues of each group were stained with hematoxylin eosin （HE） to observe the histopathology. The levels of inflammatory factors interleukin-10 （IL-10） and interleukin-17 （IL-17） in serum supernatant were detected by enzyme linked immunosorbent assay （ELISA）. Measuring the length（D₁），width （D₂） and height （D₃） of the heterotopic foci in each group before and after treatment. Then calculating the volume of them. The expression of tyrosine kinase 2（JAK2），transcription factor 3 （STAT3），phosphorylation transcription factor 3 （p-STAT3）， vascular endothelial growth factor （VEGF）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and thrombospondin-1 （TSP-1） were detected by immunohistochemistry （IHC）. The expression of VEGF，TNF-<italic>α</italic> and TSP-1 was detected by Western blot. Result:Microscopic pathological observation showed that the endometrial glandular cells of the blank group were arranged in order， and the glandular and stromal cells grew well， compared with the blank group， the endometrial structure of the model group was complete， showing a cavity like or annular closed structure， with cyst formation， and the epithelium was cubic or columnar epithelium， most of the epithelial cells had secretion， the stroma was dense， and the matrix showed a little fibrosis There were a few glands and inflammatory cell infiltration. Compared with the blank group， the content of IL-10 in serum of model group was significantly decreased （<italic>P</italic><0.01）， and the content of IL-17 was significantly increased （<italic>P</italic><0.01）， the protein expression of JAK2， STAT3，p-STAT3， VEGF， TNF-<italic>α</italic> in endometrial tissue of model group was significantly increased （<italic>P</italic><0.05）， and the expression of TSP-1 protein was significantly decreased （<italic>P</italic><0.05）. Compared with the model group， the serum IL-10 content of rats in modified Wenjingtang treatment group increased significantly （<italic>P</italic><0.01）， the IL-17 content decreased significantly <italic>（P</italic><0.01）， and the volume of ectopic foci decreased significantly （<italic>P</italic><0.01）. While the level of JAK2，STAT3，p-STAT3，TNF-<italic>α</italic>，VEGF protein in intimal tissue of modified Wenjingtang high and middle dose group decreased significantly （<italic>P</italic><0.05） and the level of TSP-1 protein increased significantly （<italic>P</italic><0.05）. Conclusion:Modified Wenjingtang can inhibit the invasion of ectopic foci in EM rats with kidney deficiency and blood stasis， the mechanism may be related to the intervention of immune barrier and block angiogenesis function mediated by JAK2/STAT3 signaling pathway activation.

Tripterygium wilfordii multiglycoside-induced hepatotoxicity via inflammation and apoptosis in zebrafish / 中国天然药物

Tripterygium wilfordii multiglycoside (GTW) is a commonly used compound for the treatment of rheumatoid arthritis (RA) and immune diseases in clinical practice. However, it can induce liver injury and the mechanism of hepatotoxicity is still not clear. This study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism involved. The 72 hpf (hours post fertilization) zebrafish larvae were administered with different concentrations of GTW for three days and their mortality, malformation rate, morphological changes in the liver, transaminase levels, and histopathological changes in the liver of zebrafish larvae were detected. The reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the levels of microRNA-122 (miR-122) and genes related to inflammation, apoptosis, cell proliferation and liver function. The results showed that GTW increased the mortality of zebrafish larvae, while significant malformations and liver damage occurred. The main manifestations were elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), significant liver atrophy, vacuoles in liver tissue, sparse cytoplasm, and unclear hepatocyte contours. RT-PCR results showed that the expression of miR-122 significantly decreased by GTW; the mRNA levels of inflammation-related genes il1β, il6, tnfα, il10, cox2 and ptges significantly increased; the mRNA level of tgfβ significantly decreased; the mRNA levels of apoptosis-related genes, caspase-8 and caspase-9, significantly increased; the mRNA level of bcl2 significantly decreased; the mRNA levels of cell proliferation-related genes, top2α and uhrf1, significantly reduced; the mRNA levels of liver function-related genes, alr and cyp3c1, significantly increased; and the mRNA level of cyp3a65 significantly decreased. In zebrafish, GTW can cause increased inflammation, enhanced apoptosis, decreased cell proliferation, and abnormal expression of liver function-related genes, leading to abnormal liver structure and function and resulting in hepatotoxicity.

Experience in prevention, diagnosis and treatment of complications after total thoracoabdominal aortic aneurysmrepair / 中华胸心血管外科杂志

Total thoracoabdominal aortic aneurysmrepair is one of the most complex operations in cardiac surgery. Patients may have spinal cord injury, disturbance of consciousness, hypoxemia, arrhythmia, acute renal injury, abdominal organ ischemia and so on after operation. Postoperative complications may occur in patients with neurological, respiratory, circulatory, digestive, urinary and coagulation systems. This paper summarizes the experience of prevention and treatment of postoperative complications based on the medical literature at home and abroad and the experience of diagnosis and therapeutic schedule in our hospital, in order to improve the prognosis.

Therapeutic experience of an 89-year-old high-risk patient with incarcerated cholecystolithiasis: A case report and literature review.

BACKGROUND: The global pandemic of coronavirus disease 2019 pneumonia poses a particular challenge to the emergency surgical treatment of elderly patients with high-risk acute abdominal diseases. Elderly patients are a high-risk group for surgical treatment. If the incarceration of gallstones cannot be relieved, emergency surgery is unavoidable. CASE SUMMARY: We report an 89-year-old male patient with acute gangrenous cholecystitis and septic shock induced by incarcerated cholecystolithiasis. He had several coexisting, high-risk underlying diseases, had a history of radical gastrectomy for gastric cancer, and was taking aspirin before the operation. Nevertheless, he underwent emergency laparoscopic cholecystectomy, with maintenance of postoperative heart and lung function, successfully recovered, and was discharged on day 8 after the operation. CONCLUSION: Emergency surgery for elderly patients with acute abdominal disease is safe and feasible during the coronavirus disease 2019 pandemic, the key is to abide strictly by the hospital's epidemic prevention regulations, fully implement the epidemic prevention procedure for emergency surgery, fully prepare before the operation, accurately perform the operation, and carefully manage the patient postoperatively.

DnaJA4 is involved in responses to hyperthermia by regulating the expression of F-actin in HaCaT cells.

BACKGROUND: Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia. METHODS: Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein. RESULTS: DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ±â€Š989.10 vs. 4272.67 ±â€Š918.50, P < 0.05). In response to hyperthermia, F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia (WT cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.34 ±â€Š0.02 vs. 0.24 ±â€Š0.01, 0.31 ±â€Š0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ±â€Š0.01 vs. 0.30 ±â€Š0.01, 0.51 ±â€Š0.02, P < 0.001, P < 0.01). WT cells restored to baseline levels observed in the unheated condition, while DnaJA4-KO cells exceeded baseline levels in the recovery. As the upstream factors of F-actin, a similar profile in rho-associated serine/threonine kinase 1 (ROCK 1) and RhoA expressions was observed after hyperthermia. While E-cadherin expression was decreased in response to hyperthermia, it was increased in DnaJA4-KO cells compared with WT cells. CONCLUSIONS: Hyperthermia affects the expression levels of F-actin in HaCaT cells. DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia. DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.

Sphingosine-1-phosphate signal transducer and activator of transcription 3 signaling pathway contributes to baicalein-mediated inhibition of dextran sulfate sodium-induced experimental colitis in mice.

BACKGROUND: Baicalein has been shown to have anti-inflammatory and anti-tumor activities. However, the mechanisms underlying its anti-inflammatory effect on colitis remain unclear. METHODS: A dextran sodium sulfate (DSS)-induced model of acute colitis was established in BALB/c mice (6-8 weeks old, weighing 18-22 g). Six groups of mice received: (1) water for 10 days (control), n = 6; (2) DSS 4% solution in the drinking water for 7 days, followed by normal water for 3 days, n = 7; (3), (4), and (5) as for group 2 plus baicalein (10, 20, 40 mg/kg) administered once daily starting on day 1, n = 6; and (6) as for (2) plus 5-aminosalicylic acid (50 mg/kg) administered once daily starting on day 1, n = 6. Body weights, stool consistency, and hematochezia were recorded, and the severity of colitis was evaluated using a disease activity index. On day 11, the mice were euthanized, and organs and blood were collected for analysis. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay; CD11b-positive cells were analyzed by immunofluorescence microscopy; expression of retinoic-acid-receptor-related orphan nuclear receptor gamma, sphingosine kinase 1 (SPHK1), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was detected by immunohistochemistry; and expression of nucleotide-binding oligomerization domain 2 (NOD2), SPHK1, sphingosine 1-phosphate receptor 1 (S1PR1), total STAT3, and p-STAT3 were detected by western blotting analysis. Inter-group differences were compared using Student's t test. RESULTS: Baicalein treatment dose-dependently reduced DSS-induced weight loss (P < 0.01 or P < 0.05), splenomegaly (P < 0.01), and colonic damage, as reflected by amelioration of diarrhea, rectal bleeding, and colonic ulceration, congestion, edema (shown as colon length, P < 0.05 or P < 0.01), and inflammatory cell infiltration. Baicalein also significantly decreased the levels of inflammatory mediators in the serum (P < 0.01) and colon, and significantly inhibited expression of NOD2 SPHK1, S1PR1, and p-STAT3 in the colon (P < 0.05). CONCLUSIONS: Baicalein treatment ameliorated colitis in mice by inhibiting S1P-STAT3 signaling, suggesting that this flavonoid might be beneficial in the treatment of colitis.

Isoniazid promotes the anti-inflammatory response in zebrafish associated with regulation of the PPARγ/NF-κB/AP-1 pathway.

OBJECTIVE: Zebrafish inflammation models were used to evaluate the anti-inflammatory activity of isoniazid (INH) and preliminarily investigate the underlying mechanism. METHODS: Local, acute, and systemic zebrafish inflammation models were established by tail cutting, copper sulfate (CuSO4), and lipopolysaccharide (LPS) endotoxin treatments, respectively, to evaluate the anti-inflammatory activity of INH. Zebrafish in the inflammatory state were exposed to different concentrations of INH (1, 2, and 4 mM) for 72 h to observe changes in the migration and accumulation of inflammatory cells and measure the reactive oxygen species (ROS) content in zebrafish after INH treatment. The transcription levels of inflammation-related genes in zebrafish from all groups were measured using real-time polymerase chain reaction (RT-PCR). RESULTS: Compared to those observed in the control inflammation model group, the numbers of migrated and accumulated inflammatory cells in zebrafish in the INH-treated group significantly decreased. INH significantly decreased the ROS content induced by LPS. Compared to that observed in the LPS model group, INH at 1 and 2 mM significantly increased the expression of PPARγ and inhibited the expression of NF-κB, iκbαa, and AP-1 as well as the inflammatory factors TNF-ɑ, TGF-ß, IL-1b, and COX-2. CONCLUSION: In this study, different zebrafish inflammation models were used to confirm that INH has anti-inflammatory activity. The associated mechanism may occur through the inhibition of ROS release, activation of PPARγ expression, inhibition of the transcriptional regulatory activity of NF-κB and AP-1, and reduction of INH inflammatory factor expression to relieve inflammation. The results of this study provide references for the clinical application of INH.

Effect of Sanggenone C on MC3T3-E1 Based on Molecular Docking Technology / 中国实验方剂学杂志

Objective::To observe the effect of sanggenone C (SanC) on the proliferation and differentiation of mouse MC3T3-E1 osteoblasts induced by dexamethasone (DEX), and to explore its mechanism. Method::Molecular docking was conducted between SanC and Runt-associated transcription factor 2(Runx2) protein structure obtained by homologous modeling. MC3T3-E1 cells were jointly treated by different concentrations of SanC (8, 16, and 32 μmol·L-1) and 1 μmol·L-1 DEX, and then cell counting kit-8(CCK-8) method was used to detect the effect of SanC on the proliferation of MC3T3-E1 osteoblasts. The alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts was determined by reagent kit and the formation of mineralized bone nodules were detected by alizarin red staining. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of Runx2, ALP and Osterix. The protein expression of Runx2 was detected by Western blot. Result::The docking score of SanC and Runx2 was -9.78.As compared with the normal group, DEX group significantly reduced the cell survival rate (P<0.01), and the greatest difference occurred on the seventh day. As compared with DEX group, SanC could significantly promote the cell proliferation of MC3T3-E1 (P<0.01), in which 32 μmol·L-1 SanC had the largest difference in proliferation rate on seventh day. As compared with the normal group, the expression of Runx2, ALP and Osterix mRNA increased to a certain extent in DEX group(P<0.01). As compared with DEX group, the expression levels of Runx2, ALP and Osterix mRNA were up-regulated in different concentration groups of SanC in a dose-dependent manner (P<0.01). As compared with the normal group, the expression of Runx2 protein in DEX group decreased significantly (P<0.05), and as compared with DEX group, the expression of Runx2 protein in cells under the intervention of SanC increased significantly (P<0.01). Conclusion::SanC can promote the proliferation, differentiation and mineralization of MC3T3-E1 osteoblasts, and the mechanism may be related to the up-regulation of Runx2 expression.

Effect of Anemarrhena Asphodeloside BⅡ on Osteoclast Differentiation Based on Molecular Docking / 中国实验方剂学杂志

Objective:To explore the effect of anemarrhena asphodeloside BⅡ (TBⅡ) on the expressions of nuclear transcription factor-κB receptor activator factor ligand （RANKL）, RANK and C-FOS genes during osteoclast differentiation. Method:Molecular docking software LeDock was used to score the docking of TBⅡ with RANKL, RANK and C-FOS. RAW264.7 was treated with soluble RANKL（sRANKL） and divided into control group, sRANKL group (model group), Icariin (Ica) group, low-dose TBIⅡ group (2 μmol·L-1), medium-dose TBⅡ group (4 μmol·L-1), and high-dose TBⅡ group (8 μmol·L-1). The corresponding kit was used to detect iconic enzyme (TRAP) of osteoclast differentiation. Total RNA was extracted by trizol method, Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expressions of C-FOS, upstream RANKL/RANK and downstream nuclear factor of activated T-cells cytoplasmic 1 (NFATC1), and osteoprotegerin OPG. Result:The molecular docking score were -11.86, -11.38, -12.34 kcal·mol-1, and there might be multiple binding sites between TBII as well as RANKL, RANK and C-FOS. Compared with the control group, the content of TRAP in model group increased significantly (P<0.01), and compared with model group, the content of TRAP in each administration group decreased significantly (P<0.01), and TBⅡ decreased the content of TRAP in a dose-dependent manner. Compared with the control group, the expressions of RANKL, RANK, C-FOS and NFATC1 increased (P<0.01), whereas the expression of OPG decreased (P<0.01) in model group. Compared with model group, the expressions of RANKL, RANK, C-FOS and NFATC1 decreased (P<0.01), while the expression of OPG increased (P<0.01) in each administration group. Conclusion:TBⅡ may inhibit the differentiation of osteoclast precursors into osteoclasts, inhibit osteoclast activity, reduce bone resorption and improve osteoporosis by regulating RANKL/RANK/C-FOS signal pathway.

Study on the effect of structural authorization on horizontal violence among operating room nurses / 中国实用护理杂志

Objective:To investigate the status of horizontal violence between structural authorization and operating room nurses, and to analyze the influence of structural authorization on horizontal violence among operating room nurses, and to provide reference for improving the occurrence of horizontal violence among nurses in operating room.Methods:From May to June 2019, a convenient sampling method was used to select 198 operating room nurses from 4 third-grade hospitals in Beijing as the research object. The general data questionnaire, structural authorization scale, and horizontal violence questionnaire were used. Questionnaire.Results:The total score of structural authorization scale was (55.37±9.78) points. The total score of horizontal violence among nurses in operation room was (54.69±9.38) points. The structural authorization was negatively correlated with the horizontal violence between nurses in the operating room ( r=-0.786, P<0.05). Conclusion:Structural authorization can affect horizontal violence among nurses in the operating room. The head nurse should construct a positive working environment that is conducive to authorization, thus effectively reducing the occurrence of horizontal violence among nurses.